Toronto—Antibe Therapeutics Inc., a leader in developing safer therapeutics for pain and inflammation, has announced the secondary endpoint data from the recent Phase 2B gastrointestinal (GI) safety study for its lead drug, ATB-346. The double-blind study was conducted in 244 healthy volunteers and was designed to demonstrate the superiority of ATB-346 in GI safety compared to naproxen, the most prescribed nonsteroidal anti-inflammatory drug (NSAID) in the United States.
ATB-346 is a hydrogen sulfide-releasing derivative of naproxen. NSAIDs are the most commonly used therapy for osteoarthritis, yet their use is associated with a high incidence of gastrointestinal ulceration and bleeding. NSAIDs are also widely used in conditions such as rheumatoid arthritis, ankylosing spondylitis, gout, and general pain reduction, with a similarly high rate of gastrointestinal ulceration and bleeding. It’s well-accepted that patients with these conditions would benefit greatly from an effective, non-addictive, GI-sparing anti-inflammatory/analgesic agent.
Antibe announced the successful completion of this study on March 20 this year with strong primary endpoint data. The primary endpoint for the study was the incidence of gastric or duodenal ulcers of at least 3 mm diameter with unequivocal depth, considered the gold standard in assessing the GI safety of NSAIDs. As previously reported, subjects on ATB-346 exhibited an ulceration rate of 2.5% versus an ulceration rate of 42.1% for subjects on naproxen at the end of the 2-week treatment period. These results exhibited a very high degree of statistical significance (p<0.0001). ATB-346 was also safe and well tolerated.
The secondary endpoints in the study were incidence of gastric or duodenal ulcers of at least 5 mm diameter with unequivocal depth; number of gastric and/or duodenal erosions and/or ulcers; incidence of dyspepsia leading to discontinuation of study treatment; changes from baseline in hematocrit levels; and changes from baseline in ex vivo whole blood thromboxane B2 (TXB2) synthesis.
No subjects treated with ATB-346 exhibited ulcers of more than 5 mm diameter (0% ulcer incidence) versus 30 subjects treated with naproxen (24% ulcer incidence), with an average of 2.5 ulcers per subject. There were a total of 4 gastric ulcers and 0 duodenal ulcers in the ATB-346 group, versus a total of 203 gastric and duodenal ulcers in the naproxen group.
The average number of gastric and duodenal erosions (which are much less significant than ulcers) in the ATB-346 group was 1.7 per subject, versus 12.7 per subject in the naproxen group.
There were no cases of dyspepsia (i.e., indigestion) leading to study discontinuation in either treatment group. There was no difference in change from baseline in hematocrit between the two treatment arms at the end of the two-week dosing period. A significant decrease in hematocrit is a potential indicator of intestinal bleeding. NSAIDs exert analgesic and anti-inflammatory effects through inhibition of cyclo-oxygenase (COX) enzyme activity. COX activity can be assessed by measuring a biomarker in the blood known as TXB2. The average baseline TXB2 values were 86 ng/mL in the ATB-346 treatment group versus 88 ng/mL in the naproxen group (no significant difference). Both naproxen and ATB-346 inhibited TXB2 synthesis by more than 94%.
John Wallace, Antibe’s Chief Scientific Officer remarked, “The secondary GI safety endpoint data for ATB-346 are consistent with the primary endpoint data, showing unequivocal superiority over naproxen. Moreover, the thromboxane data demonstrate that profound COX inhibition was achieved with ATB-346 at 250 mg once daily, fully consistent with the Phase 2A study completed in 2016 that showed excellent pain relief compared with published data for naproxen and celecoxib. We look to fully validate the effectiveness of ATB-346 in our upcoming Phase 2 dose-ranging, efficacy study.” A comprehensive review of the study will be posted on Antibe’s website in the coming weeks.